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PET-CT Response Characteristics Following SBRT for Early-Stage and Oligometastatic Lung Tumors
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Volume 93 Number 3S Supplement 2015 7.5 (range 0.8-59), per RTOG 0813 definitions 234 (25.4%) were central lesions, with no significant tumor differences between COMP and ABC cohorts. 830 (89.2%) lesions were PRIME, 101 (10.8%) were OLIGO. ABC was used significantly more for OLIGO vs. COMP (34.4% vs.8.3%, p<0.0001). Median follow-up and SBRT dose were 16.4 months (0-109.5) and 50 G/5 fractions respectively. Overall crude rate of LF was 9.9%. Use of ABC was not associated with increased LF compared to COMP: hazard ratio (HR) Z1.043 [95% CI 0.48-2.29; pZ0.92] Three-year actuarial rates of LF for ABC vs. COMP were 13.8% and 16.5%, respectively. After stratifying by OLIGO/PRIME, neither ABC nor COMP was significantly associated with LF. There is a suggestion that centrality may be associated with LF with ABC (HR Z2.087, pZ0.066). On univariate analysis, BMI, tumor size, PET SUVmax and central location were associated with failure, with size most significant. Conclusion: Although form of motion control overall did not predict for LF in lung SBRT, central location may be associated with increased LF by ABC use. Author Disclosure: G.M. Videtic: Thoracic section; International Journal of Radiation Oncology, Biology, Physics. N.M. Woody: None. C.A. Reddy: None. T. Djemil: None. K.L. Stephans: None.
3109 The Plasma Concentration of Epidermal Growth Factor Receptor (EGFR) and Overall Survival (OS) in Non-Small Cell Lung Cancer (NSCLC) Patients P. Ye,1 J. Zhao,1 N. Maihle,2 S.L. Wang,1 J.Y. Jin,2 and F.M.P. Kong3; 1 GRU Cancer Center and Medical College of Georgia, Georgia Regents University, Augusta, GA, 2GRU-Cancer Center, Georgia Regents University, Augusta, GA, 3Georgia Regents University, Augusta, GA Purpose/Objective(s): Epidermal growth factor receptor (EGFR) is overexpressed in a variety of malignant tumors including lung cancer. A circulating isoform of EGFR can be detected in the blood of patients who have nonesmall-cell lung cancer (NSCLC). Previous reports suggest that low plasma EGFR concentrations are associated with reduced survival in stage IV NSCLC post-chemotherapy. This study aimed to determine whether plasma EGFR concentration might also be associated with overall survival (OS) in stage I-III NSCLC following radiation treatment. Materials/Methods: Patients enrolled in prospective studies in which plasma samples had been collected were eligible. All patients received radiation-based treatment. Patient age, gender, ECOG score, clinical stage, pathology, smoking history, chemotherapy, and radiation therapy were all available for inclusion in this analysis. Plasma EGFR concentrations were measured using a commercial enzyme-linked immunoassay (BosterBio Inc., Pleasanton, CA) that detects the extracellular domain of EGFR. The primary endpoint was OS. Results: A total of 107 patients with median age of 65 years old, 84 male and 23 female, with stage I-III NSCLC were eligible. The median OS was 15.2 months (95% confidence interval [CI]: 19.3-27.2). The mean plasma concentration of EGFR was 35.7 ng/ml (95% CI: 33.8-37.6) in 107 NSCLC patients. After dichotomization of EGFR using median concentration of 35.14 ng/ml as a cut off, Kaplan-Meier survival analysis showed that plasma EGFR concentrations had no significant correlation with OS (95% CI: 19.3-27.2, 24.5 months vs. 22.2 months, p Z 0.973). However, multivariate analysis confirmed that gender (p Z 0.01) and clinical stage (p Z 0.047) were correlated with OS, and revealed that RT dose (p Z 0.008) was also a significant factor. No significant differences in OS were observed between high and low plasma EFGR concentrations in patients with adenocarcinoma (95% CI: 0.470-8.306, 31 months vs. NR, p Z 0.353), in patients treated with RT alone (95% CI: 0.271-2.262, 24.5 months vs. 18.2 months, p Z 0.651), or in patients treated with concurrent radiation and chemotherapy (95% CI: 0.684-2.166, 23.5 months vs. 28.1 months, p Z 0.503). Conclusion: This preliminary analysis suggests that plasma EGFR concentration may not be useful as an independent prognostic factor in stage IIII NSCLC patients treated with radiation. Further studies using a large cohort of NSCLC patients treated with radiation are ongoing.
Author Disclosure: P. Ye: None. J. Zhao: None. N. Maihle: None. S. Wang: None. J. Jin: None. F.P. Kong: Research Grant; NIH.
3110 PET-CT Response Characteristics Following SBRT for Early-Stage and Oligometastatic Lung Tumors P.A. Blumenfeld and D.J. Sher; Rush University Medical Center, Chicago, IL Purpose/Objective(s): Positron emission tomography (PET-CT) is a useful tool for evaluating the therapeutic effect of cancer treatment. However, the optimal restaging study after thoracic stereotactic body radiation therapy (SBRT) is an open question. Our study aims to document the changes in PET avidity following SBRT for early-stage and oligometastatic lung tumors. Materials/Methods: All patients with early-stage and oligometastatic lung tumors in whom diagnostic pre- and post-treatment PET-CT scans were performed and who underwent lung SBRT between June 2011 and November 2014 were included in this single-institution retrospective study. PET-CT reports were reviewed in order to determine the pre- and posttreatment maximum standardized uptake value (mSUV) of the lesion, including “complete resolution” of FDG-avidity, as well as the presence of radiographic pneumonitis (RP). Patients without residual FDG-avidity were assigned an mSUV of 1. Univariate analyses were performed to identify factors associated with percent change in mSUV and RP. Results: Fifty-six patients (median age 72) were identified, of whom 62 lesions were treated. 85.5% of patients had either early stage or recurrent tumors and 14.5% of patients were deemed oligometastatic. 42% of lesions were not biopsied prior to SBRT treatment, 19.4% of lesions were squamous cell carcinoma, 30.7% adenocarcinoma, and 7.9% other histology. The doses ranged from 4800 cGy to 6000 cGy in 3-5 fractions. The median time to PET-CT from SBRT was 14.5 weeks (interquartile range, IQR, 12.5-15.4). The pre-treatment mSUV median was 5.62 (IQR 3.27-6.90), the post-treatment mSUV median of the nodule alone was 2.15 (IQR 1-2.9) for a mean absolute and relative change of 3.48 (IQR 1.20-4.20) and 0.44 (IQR 0.22-0.68) respectively. 59.7% of patients had total resolution of the nodule (SUVZ1), 24.2% with residual hypermetabolic nodule and 16% of patients with questionable resolution. Radiographic pneumonitis was seen in 35.5% of patients. The only predictor for RP was lower lobe location (55%) compared to upper/middle lobe tumors (26.19%), Fisher, pZ0.045. Tumors with a higher pre-treatment mSUV were found to have larger relative change in mSUV (pZ0.074). No patient had grade 2 clinical pneumonitis, and only 1 of 62 lesions (crude 1.62%) treated in this analysis developed an in-field progression on follow-up. Conclusion: Although most patients experienced a significant reduction in mSUV, there was non-trivial variability in this response parameter despite only 1 in-field failure. With such low local recurrence rates, restaging PETCT is unlikely to become a useful tool in predicting primary tumor control outcomes. Author Disclosure: P.A. Blumenfeld: None. D.J. Sher: None.
3111 Patterns of Failure in Metastatic and/or Recurrent EGFR Mutation Positive NSCLC M.W. Orban,1 P. Kelly,2 J. Tseng,3 T. Johnson,3 R. Manon,3 R. Rostorfer,3 and J.M. Rineer3; 1University of Central Florida, Orlando, FL, 2UF Health Cancer Center at Orlando Health, Orlando, FL, 3UF Health Cancer Center - Orlando Health, Orlando, FL Purpose/Objective(s): Targeted therapy of EGFR positive (EGFR+) NSCLC with TKI has led to superior outcomes with less adverse effects compared to cytotoxic chemotherapy. However, progression is inevitable due to resistance to EGFR TKI. Current guidelines favor continued TKI in cases with single sites of progression managed with local therapy. The frequency of these and other progression events has not yet been described. In this study we seek to characterize the pattern of progression of EGFR+ NSCLC.
Volume 93 Number 3S Supplement 2015 7.5 (range 0.8-59), per RTOG 0813 definitions 234 (25.4%) were central lesions, with no significant tumor differences between COMP and ABC cohorts. 830 (89.2%) lesions were PRIME, 101 (10.8%) were OLIGO. ABC was used significantly more for OLIGO vs. COMP (34.4% vs.8.3%, p<0.0001). Median follow-up and SBRT dose were 16.4 months (0-109.5) and 50 G/5 fractions respectively. Overall crude rate of LF was 9.9%. Use of ABC was not associated with increased LF compared to COMP: hazard ratio (HR) Z1.043 [95% CI 0.48-2.29; pZ0.92] Three-year actuarial rates of LF for ABC vs. COMP were 13.8% and 16.5%, respectively. After stratifying by OLIGO/PRIME, neither ABC nor COMP was significantly associated with LF. There is a suggestion that centrality may be associated with LF with ABC (HR Z2.087, pZ0.066). On univariate analysis, BMI, tumor size, PET SUVmax and central location were associated with failure, with size most significant. Conclusion: Although form of motion control overall did not predict for LF in lung SBRT, central location may be associated with increased LF by ABC use. Author Disclosure: G.M. Videtic: Thoracic section; International Journal of Radiation Oncology, Biology, Physics. N.M. Woody: None. C.A. Reddy: None. T. Djemil: None. K.L. Stephans: None.
3109 The Plasma Concentration of Epidermal Growth Factor Receptor (EGFR) and Overall Survival (OS) in Non-Small Cell Lung Cancer (NSCLC) Patients P. Ye,1 J. Zhao,1 N. Maihle,2 S.L. Wang,1 J.Y. Jin,2 and F.M.P. Kong3; 1 GRU Cancer Center and Medical College of Georgia, Georgia Regents University, Augusta, GA, 2GRU-Cancer Center, Georgia Regents University, Augusta, GA, 3Georgia Regents University, Augusta, GA Purpose/Objective(s): Epidermal growth factor receptor (EGFR) is overexpressed in a variety of malignant tumors including lung cancer. A circulating isoform of EGFR can be detected in the blood of patients who have nonesmall-cell lung cancer (NSCLC). Previous reports suggest that low plasma EGFR concentrations are associated with reduced survival in stage IV NSCLC post-chemotherapy. This study aimed to determine whether plasma EGFR concentration might also be associated with overall survival (OS) in stage I-III NSCLC following radiation treatment. Materials/Methods: Patients enrolled in prospective studies in which plasma samples had been collected were eligible. All patients received radiation-based treatment. Patient age, gender, ECOG score, clinical stage, pathology, smoking history, chemotherapy, and radiation therapy were all available for inclusion in this analysis. Plasma EGFR concentrations were measured using a commercial enzyme-linked immunoassay (BosterBio Inc., Pleasanton, CA) that detects the extracellular domain of EGFR. The primary endpoint was OS. Results: A total of 107 patients with median age of 65 years old, 84 male and 23 female, with stage I-III NSCLC were eligible. The median OS was 15.2 months (95% confidence interval [CI]: 19.3-27.2). The mean plasma concentration of EGFR was 35.7 ng/ml (95% CI: 33.8-37.6) in 107 NSCLC patients. After dichotomization of EGFR using median concentration of 35.14 ng/ml as a cut off, Kaplan-Meier survival analysis showed that plasma EGFR concentrations had no significant correlation with OS (95% CI: 19.3-27.2, 24.5 months vs. 22.2 months, p Z 0.973). However, multivariate analysis confirmed that gender (p Z 0.01) and clinical stage (p Z 0.047) were correlated with OS, and revealed that RT dose (p Z 0.008) was also a significant factor. No significant differences in OS were observed between high and low plasma EFGR concentrations in patients with adenocarcinoma (95% CI: 0.470-8.306, 31 months vs. NR, p Z 0.353), in patients treated with RT alone (95% CI: 0.271-2.262, 24.5 months vs. 18.2 months, p Z 0.651), or in patients treated with concurrent radiation and chemotherapy (95% CI: 0.684-2.166, 23.5 months vs. 28.1 months, p Z 0.503). Conclusion: This preliminary analysis suggests that plasma EGFR concentration may not be useful as an independent prognostic factor in stage IIII NSCLC patients treated with radiation. Further studies using a large cohort of NSCLC patients treated with radiation are ongoing.
Author Disclosure: P. Ye: None. J. Zhao: None. N. Maihle: None. S. Wang: None. J. Jin: None. F.P. Kong: Research Grant; NIH.
3110 PET-CT Response Characteristics Following SBRT for Early-Stage and Oligometastatic Lung Tumors P.A. Blumenfeld and D.J. Sher; Rush University Medical Center, Chicago, IL Purpose/Objective(s): Positron emission tomography (PET-CT) is a useful tool for evaluating the therapeutic effect of cancer treatment. However, the optimal restaging study after thoracic stereotactic body radiation therapy (SBRT) is an open question. Our study aims to document the changes in PET avidity following SBRT for early-stage and oligometastatic lung tumors. Materials/Methods: All patients with early-stage and oligometastatic lung tumors in whom diagnostic pre- and post-treatment PET-CT scans were performed and who underwent lung SBRT between June 2011 and November 2014 were included in this single-institution retrospective study. PET-CT reports were reviewed in order to determine the pre- and posttreatment maximum standardized uptake value (mSUV) of the lesion, including “complete resolution” of FDG-avidity, as well as the presence of radiographic pneumonitis (RP). Patients without residual FDG-avidity were assigned an mSUV of 1. Univariate analyses were performed to identify factors associated with percent change in mSUV and RP. Results: Fifty-six patients (median age 72) were identified, of whom 62 lesions were treated. 85.5% of patients had either early stage or recurrent tumors and 14.5% of patients were deemed oligometastatic. 42% of lesions were not biopsied prior to SBRT treatment, 19.4% of lesions were squamous cell carcinoma, 30.7% adenocarcinoma, and 7.9% other histology. The doses ranged from 4800 cGy to 6000 cGy in 3-5 fractions. The median time to PET-CT from SBRT was 14.5 weeks (interquartile range, IQR, 12.5-15.4). The pre-treatment mSUV median was 5.62 (IQR 3.27-6.90), the post-treatment mSUV median of the nodule alone was 2.15 (IQR 1-2.9) for a mean absolute and relative change of 3.48 (IQR 1.20-4.20) and 0.44 (IQR 0.22-0.68) respectively. 59.7% of patients had total resolution of the nodule (SUVZ1), 24.2% with residual hypermetabolic nodule and 16% of patients with questionable resolution. Radiographic pneumonitis was seen in 35.5% of patients. The only predictor for RP was lower lobe location (55%) compared to upper/middle lobe tumors (26.19%), Fisher, pZ0.045. Tumors with a higher pre-treatment mSUV were found to have larger relative change in mSUV (pZ0.074). No patient had grade 2 clinical pneumonitis, and only 1 of 62 lesions (crude 1.62%) treated in this analysis developed an in-field progression on follow-up. Conclusion: Although most patients experienced a significant reduction in mSUV, there was non-trivial variability in this response parameter despite only 1 in-field failure. With such low local recurrence rates, restaging PETCT is unlikely to become a useful tool in predicting primary tumor control outcomes. Author Disclosure: P.A. Blumenfeld: None. D.J. Sher: None.
3111 Patterns of Failure in Metastatic and/or Recurrent EGFR Mutation Positive NSCLC M.W. Orban,1 P. Kelly,2 J. Tseng,3 T. Johnson,3 R. Manon,3 R. Rostorfer,3 and J.M. Rineer3; 1University of Central Florida, Orlando, FL, 2UF Health Cancer Center at Orlando Health, Orlando, FL, 3UF Health Cancer Center - Orlando Health, Orlando, FL Purpose/Objective(s): Targeted therapy of EGFR positive (EGFR+) NSCLC with TKI has led to superior outcomes with less adverse effects compared to cytotoxic chemotherapy. However, progression is inevitable due to resistance to EGFR TKI. Current guidelines favor continued TKI in cases with single sites of progression managed with local therapy. The frequency of these and other progression events has not yet been described. In this study we seek to characterize the pattern of progression of EGFR+ NSCLC.